Used with adaptive optics scanning laser ophthalmology (AOSLO), the NT-501 intraocular implant from Neurotech Pharmaceuticals (Lincoln, RI) imaged and measured the rate of the progressive degeneration of cone photoreceptors in patients with retinitis pigmentosa (RP), a condition that eventually results in blindness. AOSLO overcomes a major obstacle in the study of retinal degeneration—the noninvasive measurement of cone photoreceptor cells and their rate of degeneration in the eyes of living subjects.

In the prospective study, two patients with RP and one patient with Usher syndrome type 2, a rare genetic disorder characterized by vision loss due to RP and bilateral hearing loss, were evaluated by AOSLO at baseline and at 3, 6, 12, 18 and 24 months following implantation. Patients studied were selected from Neurotech’s Phase 2 NT-501 study in patients with early-stage RP. For each patient, one eye received an NT-501 implant—which consists of human cells genetically modified to secrete ciliary neurotrophic factor (CNTF)—while the fellow eye received sham-treatment. AOSLO quantitatively assessed photoreceptor loss by measuring cone density and average cone spacing at several prospectively identified locations in the retina of each patient, aggregating repeated measures for all data points, and comparing results for the active- and sham-treated eyes. No increase in cone spacing or decrease in cone density was observed in any of the eyes treated with NT-501. An increase in cone spacing and a decrease in cone density are both indicative of photoreceptor loss. In addition, the results demonstrated a statistically significant preservation of cone photoreceptors in the eyes of all three subjects treated with the NT-501 implant versus sham-treated eyes. Cone spacing increased by 2.9% more per year in sham-treated eyes than in NT-501-treated eyes (p < 0.001), and cone density decreased by 9.1% more per year in sham-treated eyes than in NT-501-treated eyes (p = 0.002).

Jacque Duncan, MD, Professor of Clinical Ophthalmology, University of California, San Francisco, and Austin Roorda, Ph.D., Professor of Optometry and Vision Science, Chair and Head Graduate Advisor in the Vision Science Program, University of California, Berkeley, led the study, which appears in the April 2011 issue of Investigative Ophthalmology & Visual Science.

“We are extremely encouraged by the photoreceptor preserving effect of NT-501 seen in this study as well as the usefulness of AOSLO as a diagnostic tool for retinitis pigmentosa progression," says Duncan. "Larger studies using AOSLO are urgently needed to confirm the photoreceptor protective effect of NT-501 treatment in patients with retinal degeneration.”

Paul Sieving, MD, Ph.D., Director of the National Eye Institute and Principal Investigator of Neurotech’s Phase 1 study of NT-501 in RP, commented, “These results suggest that AOSLO may play a meaningful role in the early assessment of photoreceptor loss due to retinitis pigmentosa well before serious functional loss is detected by standard measures of visual function, and that NT-501 may play an important neuroprotective role.”

“These exciting results add to the growing body of evidence that NT-501 will benefit individuals who suffer from retinitis pigmentosa and other retinal degenerative diseases,” stated Ted Danse, Neurotech's CEO. “Given the slow progression of these diseases, measuring improvements in visual function appears to require extremely lengthy trials. We believe tools such as AOSLO that measure photoceptor preservation can play an important role in defining meaningful and measurable near-term benefits of treatment of such slow-progressing, debilitating diseases."